Thermodilution is a well-known invasive procedure for enabling a physician to determine the main hemodynamic parameters of the human body. The patients investigated are admitted to the Intensive Care Unit and have pulmonary artery catheters inserted; the cardiac output direct measurements are made for clinical indications. Ice cold saline solution is used for the thermodilution measurements. This method is quite accurate, but it suffers from obvious disadvantages of an invasive diagnostic and treatment procedure.
Several non-invasive methods intended to substitute the invasive thermodilution procedure have been disclosed in the prior art. Two such modern non-invasive methods are widely known; the one method is based on echocardiographic measurements, and the second is the bioimpedance measurement method.
An obvious requirement of non-invasive techniques is the correlation of their results with the readings obtained by the basic invasive method, such as thermodilution. It has been found that the echocardiographic measurements are technically unsatisfactory in many cases.
On the other hand, the bioimpedance measurements, performed by modern impedance cardiographs, show reasonable correlation coefficients with thermodilution. (C. Jewkes and others: British Journal of Anaesthesia 1991; 67:788-794).
The validity of impedance cardiography is an important issue because of its potential usefulness in intensive care medicine. Impedance cardiography can be used in the intensive care unit to monitor changes in hemodynamic parameters (e.g. Cardiac Output, Systemic Vascular Resistance, etc.) as well as to gauge responses in these parameters to pharmacologic therapy. This technique would be most helpful for the postoperative cardiac patient, for clinical research of essential hypertension and for other cardiovascular diseases.
The bioelectric impedance of a living tissue or the whole body is the measurement of its opposition to an electric current passing therethrough between electrodes applied to the body. Different physiological activities producing variations in the value of the tissue's conductivity, cause changes in the distribution of the current density which are detected as variations in the impedance of these tissues or the whole body.
The impedance readings consist of the following three major components:
1. The base impedance (Zo) arising from the electrical characteristics of the fundamental materials which make up the tissues (mainly, the extracell fluids). PA0 2. The impedance change (.delta.Z), synchronized with the cyclic cardiac activity. This component forms a line, called the rheogram, representing the information concerning the cardiac activity. PA0 3. The impedance waveform (.delta.V), accompanying the changes of the air volume and redistribution of the blood volume caused by respiration. The combination of these three components form a curve, which is called the plethysmogram by several researchers. PA0 1. Calculation of all the main "volume" hemodynamic parameters (Stroke volume, Cardiac output, etc.) is accomplished by using the derivative of the Impedance (dZ/dt), but not the Impedance itself (Z) or its active component (R), being the direct characteristics of the fluid volume. PA0 2. Non reliable results of calculations are achieved owing to nonlinearity of the impedance and necessity to provide complicated current corrections. PA0 3. Dispersion of the measuring current out of the segment measured in the other parts of the body. PA0 4. Geometry of the particular chest or other segments is not taken into consideration. PA0 5. Errors occurring owing to the initial non-accurate electrodes' dislocation on the thorax, and their displacement caused by respiration. PA0 6. Quite high error of calculations owing to the fact, that (.delta.Z) is measured relatively to the partial, segmentary (Z) of the body, but not relatively to the total (Z) of the whole body. PA0 7. The necessity of the second channel's signal (ECG) for synchronization of the measurements, in addition to the rheogram signal, results in a plurality of electrical wires needed for the patient's examination.
Consequently, three main groups of hemodynamic parameters are reflected in the plethysmogram and thus can be calculated therefrom.
Although electrical bioimpedance measurements have been studied for more than 30 years, it is only in recent years that clinical studies have documented the applicability of the bioimpedance measurements in the clinical setting.
Two main types of the Electrical Bioimpedance Measurements (EBM) are known in the prior art:
Local (segmentary) EBM of the variations in the blood volume, provided on specific parts of the body; the technique for thoracic EBM was suggested by Kubicek and colleagues in 1966, and then modified by Shramek and Bernstein; and
Integral EBM of the whole body, enveloping practically the entire blood conducting system; the technique is described by M. Tishcenko (1968), Yakovlev (1973), Holzer (1970) and others. The integral EBM technique is a priori more informative than the segmentary EBM; however, no appropriate technical realization thereof has been recorded.
So far as the Segmentary-type of the Electrical Bioimpedance Measurements are concerned, it has been shown that Segmentary EBM employs a low level current applied to the thorax, where changes in the volume and velocity of blood flow in the thoracic aorta result in detectable changes in thoracic conductivity. Kubicek et al. demonstrated that the first derivative of the oscillating component of thoracic bioimpedance (dZ/dt) is linearly related to aortic blood flow. Using this relationship, empirical formulas were developed to estimate Stroke Volume (SV), and then Cardiac Output (CO). (Francis G. Spinale and others, Critical Care Medicine, 1990, Vol 18 No. 4, USA).
The original Minnesota Impedance Cardiograph was developed based on Kubicek's method. However, as reported by C. Jewkes and others, British Journal of Anaesthesia 1991; 67:788-794, this device produced different correlation coefficients with the thermodilution technique, varying from good (r=0.97) to poor (r=0.41).
Several achievements were then reported in the field defined by Kubicek and Shramek.
U.S. Pat. No. Re: 30,101 (William Kubicek et al.) describes an Impedance Plethysmograph. Cardiac output is measured by connecting excitation electrodes at the upper and lower ends of the thorax of a patient, and connecting measuring electrodes to the thorax between the excitation electrodes. A constant fluctuating excitation current is applied to the excitation electrodes, and any changes in impedance within the thorax are measured, whilst simultaneously measuring the beginning and the end of a systole. Cardiac output is determined by measuring the maximum decreasing impedance slope during the systole.
U.S. Pat. No. 4,450,527 (Bohumir Shramek), assigned to one of the leading companies in the field, BoMED.RTM. Medical Manufacturing Ltd., describes a non-invasive continuous cardiac output monitor. The system disclosed eliminates the effect of respiration from the thoracic impedance as a function of time, so as continuously to provide a signal of pulsatile thoracic impedance changes. The pulsatile thoracic impedance signal is processed to produce signals indicative of the ventricular ejection time and the maximum rate of change of the pulsatile thoracic impedance, which are fed to a microprocessor in order to calculate the volume of blood pumped per stroke according to an improved systolic upstroke equation.
BoMED.RTM. continued its activity in the described field and is now offering several products. One of them is the BoMED.RTM. NCCOM3 (Irvine, Calif.). It has replaced the band electrodes of the original Minnesota Impedance Cardiograph with pairs of standard ECG electrodes, which improves patients'acceptance. It also has an integrated computer using a new algorithm based on the Bernstein-Shramek formula, which allows on-line calculation of Stroke Volume (SV) and Cardiac Output (CO). (C. Jewkes and others: British Journal of Anaesthesia 1991; 67:788 794).
The device is used to measure cardiac output (CO), stroke volume (SV), heart rate (HR), and basal impedance (Zo) or thoracic fluid index (TFI). Two "sensing" electrode pairs are placed on the thorax at the level of the mid-axillary line and on the lateral aspect of the neck. The other two pairs of the "current injecting" electrodes are located 5 cm above the cervical, and below the thoracic sensing electrodes. The current injecting electrodes deliver a 2.5 mA, 70 KHz, alternating current.
The comparison of the EBM results, supplied by the BoMED.RTM. NCCOM3, with the Thermodilution readings, have shown reasonable correlation coefficients.
However, remarks concerning the BoMED.RTM. apparatus, it has been shown in several studies (C. Jewkes); (Francis G. Spinale); (Kou Chu Huang and others, Critical Care Medicine, 1990, Vol 18, No. 11), that:
the apparatus overestimates at low and underestimates at high values of cardiac output. In other words, there is no linearity in the measuring characteristics; and PA1 the apparatus is critical to the form, type and placement of the electrodes. PA1 obtaining complete information concerning cardiorespiratory parameters, which can be provided only by means of the integral EBM of the complete human body, such as: PA1 hemodynamic parameters: PA1 Respiratory parameters: PA1 and additional important parameters, such as: PA1 obtaining results of high accuracy and reproducibility when compared with the invasive Thermodilution method; and PA1 reducing the error, which may be caused by the type, construction and placement of the electrodes used in the measuring system. PA1 the current dispersion to be reduced throughout the patient's body and extremities; PA1 the main current flow to be applied to the heart and the chest part of the patient's aorta, these being the major target of the investigation; PA1 the measured integral bioimpedance of the patient's body to be increased, thus increasing the accuracy of further calculations of the needed parameters; PA1 the other two extremities of the patient to be freed for other possible treatments or patient's simultaneous activities; PA1 the influence of random movement or tremor of the patient's legs and/or hands to be reduced.
U.S. Pat. No. 4,807,638 (B. Shramek and assigned to BoMED.RTM.) continues to describe the development of the equipment, based on EBM. A non-invasive continuous mean arterial blood pressure monitor processes the electrical impedance across two segments of body tissue (thorax and legs) to provide a signal for each segment that indicates the increase in blood flow in each segment at the beginning of each cardiac cycle. The cardiac output of the patient is also measured and the cardiac index of the patient is calculated from the cardiac output.
It should be noted, that the monitor's measuring unit comprises a current source having a high frequency constant amplitude electrical current output. The second segment's appearance in the monitor reflects the necessity of obtaining more representative information concerning the human body's hemodynamic parameters. However, the second segment's readings cannot substitute for the integral picture of the human body's hemodynamic parameters. The electrodes, used in the monitor, are arranged on the two segments in the way described in the previous reference. It means that an unpredictable error will appear due to each pair of the excitation and measuring electrodes and due to the distance between these pairs.
The regular segmentary thoracic EBM method and the same disposition of the excitation and measuring electrodes are used in the new BoMED.RTM. model 2001 Hemodynamic Management System HDMS. A constant magnitude alternating current having a frequency of 70 KHz and a magnitude of 2.5 mA flows through the thorax. The apparatus does not demonstrate any revolutionary approach to the problem.
Analyzing the systems, which implement Kubicek's and Shramek's method, it should be noted that they are not accurate for the following reasons:
Moreover, these systems do not obtain and calculate parameters, characterizing the respiratory system.
One of the latest local EBM techniques which have been recently developed is described in U.S. Pat. No. 5,178,154 assigned to Sorba Medical Systems, Inc. There is disclosed an impedance cardiograph and method of operation thereof, utilizing peak aligned ensemble averaging which provides high measurement accuracy.
However, the Sorba system still suffers several drawbacks. Thus, in the first instance, the measurements are provided by a tetrapolar system of electrodes which is complex, inconvenient to the patient and results in artifacts.
Secondly, the main parameter to be measured (Cardiac Stroke Volume) is computed by the Sorba system from a limited area section under a line of the mathematical derivative of the bioimpedance curve of a cardiac cycle. More particularly, this area reflects only the phase of the fast ejection of blood by the heart, and thus cannot reflect all specific processes of blood distribution taking place during a complete cardiocycle (and having an influence on the cardiac parameters).
Thirdly, owing to the fact that the Sorba system provides the thoracic impedance measurements, signals characterizing cardiac activity are much weaker (10%) than carrier signals of respiratory cycles; however, the small cardiac activity signals in Sorba's system are thoroughly sorted out, averaged and processed, while the respiratory oscillations are considered as artifacts and are not analyzed. It is understood, that when using such an approach the respiratory parameters cannot be defined, and the accuracy of calculations of cardiac parameters may be difficult to achieve.
Also known is the so-called Integral EBM of the whole body, enveloping practically the entire blood conducting system. This technique is described by M. Tishcenko (1968), Yakovlev (1973), Holzer (1970) and others. The integral EBM is a priori more informative than the segmentary EBM; however, no appropriate technical realization thereof has been recorded.
The Integral EBM of the whole body was originally suggested by M. Tishcenko (for example, Tishcenko M. I.: The biophysical and integral basis of integral method for determination of stroke volume of human blood system; Abstract of Ph.D. dissertation, Moscow, 1971). This method includes applying electrodes not to a segment, but to the whole human body; conveying a low alternating current having a frequency of 30 KHz, passing through the whole body; measuring the whole body's impedance with a rheograph having a measuring bridge; separation of the active component of the impedance by manual tuning, and using it for the subsequent calculations.
The integral EBM method thus described enables the operator to obtain information, concerning the whole cardiovascular system of the body; the main hemodynamic parameters are obtained using different empiric equations derived by M. Tishenko for the integral measurements. Owing to the larger length of the body, embraced by the electrodes, calculation errors can be minimized. The method uses a bipolar electrode system, which is simpler and less prone to error than the tetrapolar Kubicek's system used in the segmentary type EBM method.
However, the system used by M. Tishcenko, needs to be calibrated before every measurement; it also requires tuning in order to exclude the reactive component of the impedance. The other problem is the error, caused by the reactive component, appearing between the electrodes and the skin at the place of their contact. This error is almost impossible to remove by tuning. The accuracy of the calculations completely depends on the manual adjustment, thus rendering the Tishcenko system unreliable.
Research accomplished by the applicant prior to making the present application was intended to satisfy the requirements of modern clinical investigations, such as:
Stroke Volume PA2 Systolic Index PA2 Pulse rate PA2 Cardiac output PA2 Heart Index PA2 Reserve Index PA2 Total Resistance Index PA2 Index of Tone Stabilization; PA2 Rate of respiration PA2 Index of Respiration changes PA2 Index of Respiration intensiveness; PA2 Index of Hemodynamic Security; PA2 Volume of Extracell Fluid of the whole body PA2 Index of Fluid balance of the whole body;
The non-invasive method and system, which were investigated by the applicant, were effected by applying four electrodes to the extremities of a patient's body, introducing an alternating current via the four electrodes through the patient's body; further obtaining the integral impedance curve of the human body from these electrodes; and applying a computerized calculation of the cardiorespiratory parameters of the complete patient's body and parameters concerning the extracell fluids of the patient's body from the integral bioimpedance curve, using empiric formulae applicable to integral bioimpedance measurements.
However, when performing measurements with the above-mentioned four electrodes system, a relatively weak integral bioimpedance signal is still received from the human body.
One reason for this effect is that the measuring current is dissipated over a plurality of the chest arteries of the patient, as well as over the four of the patient's extremities, acting like parallel branches of the electric circuit. Secondly, the measuring current flow which passes through the human's body in the four electrodes system is not mainly directed through the real targets of the measurements, such as the heart and the chest part of the patient's aorta.
These two factors have a negative influence on the reliability of the measurements. Moreover, four electrodes which are to be applied to the human body, still cause a certain amount of inconvenience to the patient and to the operator.